Document R2B9eZQnYw56nGR1jV1BbqR78

FILE NAME Talc TALC DATE 1956 DOC TALC109 DOCUMENT DESCRIPTION Medical Journal Article - Massive Pulmonary Fibrosis from the Inhalation of Talc Thorax 1956 11 287 MASSIVE PULMONARY FIBROSIS FROM OF TALC THE INHALATION BY A. C. HUNT From the Department of Forensic Medicine The London Hospital Medical College RECEIVED FOR PUBLICATION FEBRUARY 4 1956 It is generally accepted that the inhalation of commercial talc powders can occasionally produce pulmonary disease This is usually fibrosis of a nodular type and only a few examples of massive fibrosis have been reported most of them without pathological description This is the report of one such case showing certain unusual features CASE REPORT charging and occasionally in amount of talc dust to which these years was negligible plate casting The he was exposed for CLINICAL HISTORY the gross radiological changes his physical state was remarkably good He first came under observation as an patient of the Miller General Hospital Greenwich nine years before his death when he was examined because his son developed pulmonary tuberculosis During the last " 10 years of his life he had several attacks of bron- chitis with cough and sputum and pyrexia These INDUSTRIAL HISTORY patient was 57 years were treated at home with early recovery Apart old at his death He joined the Army at the age of 16 at the start of the first world war During this war he was gassed although not severely When he left the Army he became a storekeeper in a food store In 1927 at the age of 29 he first entered the from these attacks he had a slight morning cough productive of a jelly greyish sputum He was not breathless on normal exertion Nine months before death all the phalangeal joints of both hands became swollen and painful with slight accumulator industry For the first six years he was employed in lead burning and was not exposed to dust After this he joined another firm as a plate caster The following 10 years i.e. between the ages ulnar deviation of the fingers The left ankle was transiently swollen There was no spindling of the interphalangeal joints and at this time there was early clubbing of the fingers His hands were radiographed of 35 and 45 was the only period during which he when he was first seen to exclude the bony changes was exposed to dust Lead accumulator plates were of sarcoidosis and again together with other joints A cast in a operated mould consisting of two when the knuckles became swollen None of these faces hinged at the bottom There were two men cast- radiographs showed any bony abnormality Clini- ing in one small room each with his own mould and cally the joint changes were considered to be mani- with a communal fired lead pot The mould was festations of pulmonary osteoarthropathy Unfor- oa at about waist height It was opened and then each tunately no joints were examined histologically after coer surface was roughly dusted with talc from a loosely woven calico bag or an old sock The bag was death and it is impossible to exclude rheumatoid arthritis It would have been of interest to make banged hard against the mould and a cloud of dust would arise Next the mould was closed and the this exclusion in view of Caplan's 1953 observation of the modification of miners pneumoconiosis in lead poured in It was cooled with water and opened and the plate removed The sequence was then repeated The patient was a good workman and cast up to 110 plates an hour being paid piece rates The talc bag contained about quarters of a pound of talc and about three bags were used in two days There was no dust extraction in the room and every- men with rheumatoid arthritis The only physical signs recorded in the chest during the period of observation were occasional r^lesespecially over the right lung Sputa were examined for tubercle bacilli by microscopy and culture repeatedly during these nine years Between four and six groups of sputa were examined yearly and no tubercle bacilli were thing was covered with talc dust The source of the talc used cannot be traced except for the last two years ever found The sedimentation rate was estimated at regular intervals and was on most occasions moder- of this period when it was obtained from Manchuria Canada or Egypt The plates are now cast ately raised but sometimes normal The Mantoux reaction was positive at a dilution of 10,000 An automatically in this factory and the mould faces are dressed with a cork compound; there is no dust risk whatever electrocardiograph taken three months before death showed no definite right ventricular preponderance An axillary lymph node was removed for biopsy six After 10 years of this work the patient was engaged for 12 years before his death in battery assembly and years before death to investigate the possibility of sarcoidosis There were a few doubly refractile A. C. HUNT FIG Radiograph of chest nine years before death particles in the lymphatic sinuses resembling the talc particles found in the lung at necropsy but no other abnormality During the last year of his life he had occasional fainting attacks on exertion On the day FIG Radiograph of chest seven years before death of his death he had dug potatoes in the morning eaten a large lunch Shortly after the meal he found dead in a lavatory having defaecated He seen to be quite well immediately before this and was was FIG Radiograph of chest five years before death FIG Radiograph of chest two months before death MASSIVE PULMONARY FIBROSIS DUE TO TALC INHALATION RADIOLOGICAL APPEARANCES Figs 1-4 were taken of the chest at intervals of three to four months throughout the last nine years of his life In the earlier films there were numerous faint small opacities average diameter 0.3 cm scattered throughout the lung fields They were most closely set around the borders of the cardiac shadow and the hila in the anterior views In the right lower and middle zones were four defined larger mottled opacities each about 2 cm diameter There were several similar smaller opacities in the left lower lobe There was no evidence of cavitation at this time During the succeeding years the larger opacities increased in size and gradually became confluent Those in the left lower lobe had become a single large mass 7 by 4 cm within four years By this time also the first signs of cavitation in the confluent opacities in the right lower and middle zone had appeared The smaller nodules also enlarged and lost their discrete outline producing a lattice picture By the time of death there were large opacities occupying the middle thirds of both lung fields and the cavities in the right middle zone could be clearly seen The lower edge of the opacity in the right lung had assumed a stellate pattern with dense streaks extending towards the distorted diaphragm The heart shadow was not appreciably enlarged and the trachea remained central MORTEM EXAMINATION body was that of a fairly well nourished man There was slight 289 FIG Sagittal section ofleft lung FIG Sagittal section of right lung swelling of the phalangeal joints but no spindling of the interphalangeal joints There was slight clubbing of the fingers The right ventricle was slightly hypertrophied only 0.5-0.6 cm thick in the conus and not dilated The heart weighed 340 g The valves were normal There were a few flecks of atheroma in the pulmonary arteries The other organs were normal There was nothing to account for his sudden death apart from the changes in the lungs and it was considered that death had occurred from acute cardiac failure There were dense fibrous adhesions over all surfaces of both lungs and partial obliteration of the of the left lung Both lungs were firm and the left weighed 1,030 g and the right 915 g fissures heavy; Left Lung Fig There was a hard mass in both lobes reaching the hilum not involving the apical segment of either lobe and reaching to within 2 cm of the pleura of the anterior and lateral surfaces and to about 4 cm of the posterior surfaces The cut surface of the mass was whitish with paler bands running through it There were a few islands of greatly emphysematous firm lung in the mass and the outer edge was roughly lobulated Especially at the periphery individual nodules up to about a centimetre in diameter could be identified by palpation There was an irregular cavity in the fibrous mass in 290 A. C. HUNT visible with the naked eye in the fibrosis in the upper lobe and there were similar nodules in the remaining lung as in the left lung and the centres of many of these were also friable HISTOLOGY throughout the confluent masses were thick cellular seams of macrophages and formed multinucleate giant cells of a foreign body type Fig 7 The giant cells and most of the macrophages were packed with doubly refractile particles when viewed by polarized light Fig 8 These particles were predominantly shaped and 5-10 ... long The seams were broadest at the peri- phery of the masses where they were up to 0.5 cm in diameter and varying from a few millimetres to a centimetre or more apart The rest of each mass was fibrous tissue containing large areas of necrosis Some of these areas were composed of amorphous finely granular material stained yellow with van Gieson's stain and pink with eosin Sometimes surviving macrophages were present at the edges and a few poorly fuchsinophil strands were still visible Doubly refractile particles were present in large numbers often greatest at the periphery Fig 9 In places the amorphous material was in aggregates the size and shape of necrotic cells and these areas appeared to have been formed by necrosis in the Prag FIG Giant granulomatous seam ^ 130. Haematoxylin and eosin the upper lobe 8 by 5 by 3 cm the long axis of which ran posteriorly The wall of the cavity was trabeculated and the lining rough and slightly gritty to the touch The centre of the fibrosis in the lower lobe was breaking down in an area of about 4 cm diameter where it was of similar colour to the remaining fibrosis but friable The remaining lung was emphysematous and scattered in it were illdefined firm nodules varying from a pin's head to 1.5 cm in diameter The centres of most of these larger nodules were also soft and friable slight diffuse cylindrical bronchiectasis There was throughout the lung Right Lung Fig There was a similar mass extending from the hilum to within 3 cm of the pleura of the posterior surface but reaching the pleura of the lateral surface of the lower lobe The mass was more obviously nodular than on the left The fibrosis appeared denser around the larger bronchi especially in the lower lobe There was a cavity 9 by 3 cm in the mass in the lower lobe mainly in the anterior basal segment It consisted of a honeycomb of interconnecting large spaces with a smooth shiny black lining There was a smaller cavity in the right middle lobe which was similarly lined except for a few areas in which the lining was rough and granular Small patches of necrosis were Fig Giant cells laden with doubly refractile particles Photograph obtained by exposure with and without polarization of light Haematoxylin and eosin ^ 650. MASSIVE PULMONARY FIBROSIS DUE TO TALC INHALATION 291 Perles's reaction and for calcium by von Kossa's method Throughout the fibrous parts of the lungs were a few macrophages containing free iron and there were small particles in the cavitated necrosis The cavities in the right lung were similar to those in the left upper lobe except that there was a thin layer of fuchsinophil collagen superficial to the necrotic and cellular elements and forming the smooth lining The earliest lesions in the remaining lung were small interstitial cellular foci containing fine collagen strands mostly related to small vessels Fig 10 There were also patches of diffuse interstitial fibrosis often associated with smaller nodules The larger discrete nodules were similar to the confluent masses The fibrous tissue forming them was not whorled and the centres were frequently necrotic In these discrete nodules the foreign body giant reaction was not so marked a feature Curious bodies McLaughlin Rogers and Dunham 1949 similar but not identical to asbestos bodies have been described in most cases of talc pneumo- coniosis They consist of a single fibre with terminal rosettes but without intermediate beading They were present in this case although in small numbers Fig 11 No acid bacilli were seen in any of the sections FIG Areas of necrosis and loss of staining in collagen Van Gieson ^ 110 photographed as Fig 8. cellular seams Apart from this frank necrosis there were widespread large patches in the fibrosis where the collagen fibres were swollen and blurred stained pale orange with van Gieson's stain and were separated by similar amorphous debris to that in the areas mentioned above and also contained doubly refractile material None of the necrotic patches stained posi- tively for fibrin and the periodic reaction was negative There was a fine network of argyrophil fibrils in most of the necrotic areas Especially at the periphery of the masses and in relation to the blood vessels the fibrosis was not necrotic and often the bundles of collagen were broken up by intervening narrow bands of cells usually containing talc particles The blood vessels in relation to the fibrous masses showed severe end- arteritis fibrosa and some smaller vessels entirely permeated by fibrosis could be picked out by the remains of their elastic tissue Only a few fragments of the remains of alveolar elastic tissue were found in the fibrosis except at the periphery The cavities in the left lung were lined by necrotic debris except in a few places where collections of laden phago- cytes formed the wall Scattered in the necrosis around the cavities were numerous strongly basophilic roughly spherical granular bodies up to half a millimetre in diameter stained intensely for free iron by aS 2 FIG Early lesion in relation to blood vessel ^ 110 photographed as Fig 8. Van Gieson 292 HUNT RIGHT LUNG ho| PURE TALC | LEFT LUNG FIG ray diffraction patterns of lung residues copyright Crown the strongest quartz line at 3.34 A. This indicates that the sample contained apart from talc less than 0.5 of quartz and perhaps 2 or % of kaolin Fig 12 There was no evidence of the presence of tremolite Comparison of the talc from the lungs with samples of known origin showed a likeness to those from Egypt Italy or China but not to those from Norway Sweden U.S.A. Canada Austria India or the French Pyrenees Partial chemical analysis gave the following results : FIG Asbestos body Perles's iron reaction x 490. SO MgO Ign loss Al FO TO CaO Lung Residue 59.3 29.5 6.2 1.0 1.0 0-3 0.3 97.6 Talc Theoretical 63.4 31.8 4.8 100.0 There was diffuse alveolar emphysema throughout the surviving lung tissue and the alveolar ducts and bronchioles were dilated There were talc particles in the sinuses of the hilar glands and some of the intrasegmental glands were largely replaced by fibrosis and containing macrophages This agrees with over 90 of talc Electron photomicrographs showed typical talc plates and the diameters of the largest particles were of the order of 10 to 15 ... Fig 13 There was no evidence of erosion of the surfaces of the plates DISCUSSION MINERALOGICAL EXAMINATION AND ANALYSIS Dr. G. Nagelschmidt of the Safety in Mines Re- search Establishment Ministry of Fuel and Power examined large samples of formalin material from all lobes which represented the various consistencies of lung tissue in roughly proportional amounts to the complete lungs The dust was iso- lated by treatment with concentrated hydrogen peroxide followed by washing with alcohol and 10 HCl The weight of the dust recovered in this way was 16-17 of the dry weight or 3.5 of the wet weight With the total wet weight of both lungs of 1,945 g this would correspond to 68 g of dust The dust was pale grey and lost only % on prolonged ashing at 380 ray diffraction diagrams showed a strong talc pattern and a few weak kaolin lines and very faintly Commercial talc is a mixture of the pure mineral talc hydrated magnesium silicate with related minerals such as dolomite serpentine anthophyllite and tremolite The amount of pure talc in commercial specimens is very variable Very few samples contain any free quartz Most cases of pneumoconiosis from such minerals have been reported in miners and millers of talc The majority of studies are of clinical and radiological findings and only a limited number of descriptions of the pathological changes are available In 1934 Merewether found radiographic appearances suggestive of diffuse interstitial fibrosis in 11 workers in rubber tyre manufacture In a survey of two talc mines in Georgia Dreessen and Dalla Valle 1935 found 16 men with radiologi- MASSIVE pulmonary fibrosis due tO TALC InhalatioN 293 FIG Electron photomicrographs of residue from lung ^ 4,000 Crown copyright cal changes Porro Patton and Hobbs 1942 described the necropsies of five of 15 cases diagnosed radiologically in the Georgia mines There were poorly outlined bands and nodules of fibrous tissue infiltrated with macrophages throughout the lungs greatest in the middle lung fields Mineralogical and chemical studies are not given Soft haziness and finely granular or nodular appearances most marked in the lung fields and the bases were observed in the radiographs of 32 of 221 workers in the tremolite talc mines of St. Lawrence County New York by Siegal Smith and Greenburg 1943 They also described peripheral talc plaques in 6.3 of the whole series Slight changes were seen in 35 of 90 workers in the talc mines of Ariege Sorel Lasserre and Salvador 1943 These authors considered that talc pneumoconiosis occurred only if the lungs were previously damaged and included war gassing as one such cause It is of possible significance that this man was gassed in the first world war Fine punctate shadows were present in the chest radiographs of five of 21 accumulator plate casters examined by Reichmann 1944 and in a further seven there were mesh markings and enlarged hilar shadows Perry 1947 showed mainly peripheral and basal small nodular shadows in the lungs of two men exposed to talc in a rubber tyre factory Similar cases have been described in the cosmetic industry Millman 1947 Shatalov 1954 in textile workers Mann and Deasy 1954 and in a parachute rigger Lyons 1953 The radiographic appearances of massive fibrosis have been re- ported by Cavigneaux Charles Fuchs and Tara 1950 in a woman in a rubber works ; by Pruvost 1946 in a couturier; and Even Sors and Col- bert 1952 in two workers exposed to talc Alivasatos Pontikakis and Terzis 1955 described three cases occurring after only 18 months two and three years exposure respectively in talc factory workers in Greece The first example of talcosis in the British literature confirmed by pathological and mineralogical examination was that of McLaughlin and others 1949 This was in a workman in a rubber factory who died of rheumatic heart disease There were nodular small fibrocellular aggregates throughout the lungs containing numerous doubly refractile short shaped fibres which the authors considered to be an unusual form of talc particle It has been pointed out by Nagelschmidt 1956 that in fact the shaped particles were those of the normal flat talc plates which were standing on edge in the sections those lying flat not being visible with a polarizing microscope This phenomenon was also seen in the case described here Despite the acicular form of the particles in polarized light the electron microscope showed the usual plate forms of the mineral There was a negligible amount of free silica and numerous asbestos bodies The most comparable case in the literature is that of Di Biasi 1951 A man of 54 had been exposed to talc under similar circumstances in casting accumulator plates for 17 years At the end of this time he became progressively disabled by dyspnoea and died in congestive heart failure There were small nodules throughout the lungs and masses reaching the size of an orange in the lower parts of the upper lobes and the upper parts of the lower lobes Histologically the fibrous masses contained large structureless areas in which were large numbers of talc particles The talc plates were of the average size of 4 p, with some up to 10 and a few to 20 ...in diameter No free silica was found chemically or by ray diffraction in these lungs There was no cavitation A few " atypical tubercles are mentioned as being pre- sent Beintker and Meldau 1949 studied material from Di Biasi's case and showed erosion 294 A. C. HUNT of talc particles from the lung compared with those inhaled This was not seen in the present case An unusual syndrome was described in one patient by Jaques and Benirschke 1952 In addition to fibrocellular masses up to 4 cm diameter in the lungs there were celled granulomata in the myocardium and in the gastric mucosa Despite a heavy exposure to talc finishing eight years before death hardly any talc was found in the lesions The authors thought that sarcoidosis could be ruled out The tuberculin known that this may occur in other tissues as a reaction to talc such celled granuloma having been found in the peritoneal cavity after laparotomy and in a variety of other situations Talc has been used to promote pleural adhesions Bethune 1935 and a similar histological picture may be found after this procedure Hinson 1956 Although macrophage reaction formed giant cells have been present in most cases of talc pneumoconiosis described it does not appear to have formed the celled granuloma to the same extent as in this case skin test had been negative and no evidence of tuberculosis could be found at necropsy Recently Schepers and Durkan 1955 have reported mortem studies of the lungs of seven miners and one miller of talc Only two of these had no concomitant exposure to quartz Those with massive collagen formation were those with the highest quartz contents in the lungs They found cellular and stromal necrosis in the masses which they suggested might be due to histoplasmosis although there was no evidence that this was so There were numerous fibres 20-50 M long and many asbestos bodies Schepers suggests that both were derived from tremolite which was present in large quantities with the talc deposits of that district Schepers also published the results of dusting experiments in animals carried out at the Saranac Lake Laboratories These showed that on intratracheal insufflation in guinea tremolite SUMMARY A man who had been exposed for 10 years to talc dust developed radiological evidence of pul- monary fibrosis This later became confluent and cavitation appeared The degree of disability was negligible in comparison with the state of the lungs The clinical course and necropsy findings are described My thanks are due to Dr. H. V. Morlock M.C for permission to publish the clinical findings and radiographs to Dr. Kenneth Perry Dr. K. F. W. Hinson and Dr. Francis Camps for reading the draft and for their kind advice to Dr. G. Nagelschmidt for the mineralogy and his great interest to Mr. R. A. Kimber for the technical work and photo- graphy; and to the Ministry of Fuel and Power for permission to publish Figs 12 and 13 was actively cytogenic and fibrogenic especially in long fibre form 20-50 ...Pure talc was found to be mainly cytogenic He suggests that tremolite may be the agent responsible for pneumo- coniosis from commercial talc However neither in the case reported here nor in that of Di Biasi was any tremolite found and in both there were relatively few asbestos bodies An unusual aspect of the case being reported was the development of cavities Their appearance suggested that they may have formed by confluence of the necrotic areas so prominent in the fibrous masses The role of tuberculosis can- not be definitely assessed Acid bacilli were never found during the time the cavities were developing and there was no evidence of tuberculosis histologically On the other hand one of the patient's sons developed tuberculosis although possibly coincidentally It is possible that necro- sis and subsequent cavitation could be explained on the basis of ischaemia to which the vascular changes might contribute Another feature was the prominence of the foreign body cellular reaction It is now well REFERENCES Alivisatos G. P. A. E. and Terzis B. 1955 Brit J. MedPontikakis industr Meldau BeintkeEr. and Bethune N. 1243 R. 1949 Klin Wschr 27 07 J. thorac Surg 4 251 1935 Caplan A. 1953 Thorax 8 29 . Cavigneaux A. Charles A. Fuchs S. and Tara S. 1950 Arch Mal prof 11 34 Di BiasWi. 1951 Dreessen W. C. and paMt.h Virchows Arch Dalla ValleJ. Anat 1935 31 Pu9b505lHlth Rep Wash 50 131 C. Even R. Sors and ColbertJ.1952 Sem H^p K. W. 1956 communication F. Personal Hinson A.M.A. BenirschkeK. 1952 Paris 28 2936 A.M.A. Arch industr Jaques W. and , 5 1953 H. LyonsH. A. Milit Surg 113 393 McLaughlin and A. I. G. E. , Dunham K. C. 1949 Rogers Brit J. industr 6 184 Med1954 Merewether Chief Mann B. and DeasyJ. E. R. A. 1934 Brit med J. 2 1460 Ann Report of the Inspector of Factories for 1933 p 63. London Report of the Chief Inspector of Factories for 1935 Ann 1934 65 1947 Nagelschmidt Millman N. Occup Med 4 391 G. 1956 Personal communication K. Perry M. 1947 Thorax 2 91 Porro F. W. Patton J. R. and Hobbs A. A. 1942 Amer J. Roentgenol Pruvost P. 47, 507 Bull Acad M^'dParis 130 202 1946 ArchGewerbepGaetwehrbepath ReichmannG.V.1W.944 Schepers , industr Hlth H.182 Siegal W. Smith and31Durkan 7 Gewerbehyg 12 317 M. 1955 A.M.A. Arch , and Greenburg L. 1943 Industr Bull Shatalov 1943 R. N.Y. 224434 34 N. N. 1954 Gigiena No. 2 Sorel R., Lasserre J. and Salvador Bull Soc m^'d Hop Paris 59 267